高对映异构体过量(ee)的手性化学品的不对称合成对制药工业至关重要,但是经典的化学通常需要多步反应,恶劣的条件,和昂贵的手性配体,并且有时遭受不令人满意的对映选择性。酶催化是一种更绿色、对映体选择性更强的替代方案,和级联生物转化与多步骤反应可以在一个锅中进行,以避免昂贵的中间分离和减少废物产生。酶促级联转化的最有吸引力的应用之一是以高产率和ee将容易获得的简单外消旋底物转化为有价值的功能化手性化学品。这里,我们回顾了建立这种级联生物转化的三种一般策略,包括对映会聚反应,动态动力学分辨率,以及手性的破坏和重新安装。使用外消旋底物如外消旋环氧化物的级联转化的例子,酒精,羟基酸,等。生产手性氨基醇,羟基酸,胺和氨基酸。产品浓度,ee,和产量,可扩展性,对这些酶促级联的底物范围进行了严格的审查。为了进一步提高级联的效率和实际适用性,使用最新的基于微流体的超高通量筛选和人工智能指导的定向进化来增强关键酶的催化活性的酶工程可能是有用的方法。
Asymmetric synthesis of chiral chemicals in high enantiomeric excess (ee) is pivotal to the pharmaceutical industry, but classic chemistry usually requires multi-step reactions, harsh conditions, and expensive chiral ligands, and sometimes suffers from unsatisfactory enantioselectivity. Enzymatic catalysis is a much greener and more enantioselective alternative, and cascade biotransformations with multi-step reactions can be performed in one pot to avoid costly intermediate isolation and minimise waste generation. One of the most attractive applications of enzymatic cascade transformations is to convert easily available simple racemic substrates into valuable functionalised chiral chemicals in high yields and ee. Here, we review the three general strategies to build up such cascade biotransformations, including enantioconvergent reaction, dynamic kinetic resolution, and destruction-and-reinstallation of chirality. Examples of cascade transformations using racemic substrates such as racemic epoxides, alcohols, hydroxy acids, etc. to produce the chiral amino alcohols, hydroxy acids, amines and amino acids are given. The product concentration, ee, and yield, scalability, and substrate scope of these enzymatic cascades are critically reviewed. To further improve the efficiency and practical applicability of the cascades, enzyme engineering to enhance catalytic activities of the key enzymes using the latest microfluidics-based ultrahigh-throughput screening and artificial intelligence-guided directed evolution could be useful approaches.